Vertex Initiates First Phase 3 Study of VX-659, Tezacaftor and Ivacaftor as a Triple Combination Regimen for People with Cystic Fibrosis

-Study designed to support submission of New Drug Application in the
U.S. based on 4-week primary efficacy endpoint and 12-week safety data-

Vertex
Pharmaceuticals Incorporated (NASDAQ:VRTX) today announced that it
is initiating the first Phase 3 study of VX-659, tezacaftor and
ivacaftor as an investigational triple combination regimen for people
with cystic fibrosis (CF) who have one F508del mutation and one
minimal function mutation. The study will enroll 360 patients, and the
primary endpoint of the study is the mean absolute change from baseline
in percent predicted forced expiratory volume in one second (ppFEV1)
at week four of treatment. The study is designed to support the
submission of a New Drug Application (NDA) in the U.S. using data from
the 4-week primary efficacy endpoint together with safety data through
12 weeks of treatment.

"Our goal is to bring the best triple combination to patients as rapidly
as possible, and this first Phase 3 study of VX-659 in combination with
tezacaftor and ivacaftor is a significant step toward that goal," said
Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical
Officer at Vertex. "We're pleased to initiate this study and look
forward to working closely with the CF community to advance our two
different triple combination regimens through Phase 3 development."

"There is a significant unmet medical need to treat the underlying cause
of CF for those with one F508del mutation and a minimal function
mutation, and these patients are eagerly awaiting new treatment
options," said Steven M. Rowe, M.D., M.S.P.H., Director of the Gregory
Fleming James Cystic Fibrosis Research Center, University of Alabama at
Birmingham, and co-chair of Vertex's Triple Combination Steering
Committee. "The Phase 2 data for the triple combination of VX-659,
tezacaftor and ivacaftor showed impressive improvements in multiple
measures of CF for patients with minimal function mutations, and I am
pleased that this Phase 3 study is designed to enable rapid advancement
of the VX-659 regimen toward patients."

About the Phase 3 Study

The randomized, double-blind, placebo-controlled Phase 3 study will
evaluate VX-659 in combination with tezacaftor and ivacaftor, or triple
placebo, in approximately 360 patients ages 12 and older who have one F508del
mutation and one minimal function mutation. A list of the minimal
function mutations currently included in this study can be found here.
The primary endpoint of the study is the mean absolute change in lung
function (ppFEV1) from baseline at week four of triple
combination treatment compared to placebo.

The study is designed to support the submission of an NDA to the U.S.
Food and Drug Administration (FDA) based on data from the 4-week primary
efficacy analysis and on safety data through 12 weeks of treatment. The
study will evaluate VX-659 in combination with tezacaftor and ivacaftor
for a total of 24 weeks of treatment to generate additional safety data
and data for key secondary endpoints, including the number of pulmonary
exacerbations, change in body mass index, change in sweat chloride, and
changes in patient-reported outcomes as measured by the respiratory
domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), among
others. The 24-week data from this study are not required to complete
the NDA submission. Data from this study will also be used to support
planned regulatory submissions in Europe and other regions.

The study will evaluate a fixed-dose combination of VX-659 (240 mg),
tezacaftor (100 mg) and ivacaftor (150 mg) in the morning followed by
ivacaftor (150 mg) in the evening. An open-label extension study will be
conducted where all eligible patients, including those who received
placebo, will receive the triple combination regimen for up to an
additional 96 weeks.

CF is a rare, life-shortening genetic disease affecting approximately
75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing CFTR protein resulting from
mutations in the CFTR gene. Children must inherit two defective CFTR
genes — one from each parent — to have CF. There are approximately 2,000
known mutations in the CFTR gene. Some of these mutations, which
can be determined by a genetic test, or genotyping test, lead to CF by
creating non-working or too few CFTR proteins at the cell surface. The
defective function or absence of CFTR protein results in poor flow of
salt and water into and out of the cell in a number of organs. In the
lungs, this leads to the buildup of abnormally thick, sticky mucus that
can cause chronic lung infections and progressive lung damage in many
patients that eventually leads to death. The median age of death is in
the mid-to-late 20s.

About Vertex

Vertex is a global biotechnology company that invests in scientific
innovation to create transformative medicines for people with serious
and life-threatening diseases. In addition to clinical development
programs in CF, Vertex has more than a dozen ongoing research programs
focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex's headquarters is now
located in Boston's Innovation District. Today, the company has research
and development sites and commercial offices in the United States,
Europe, Canada and Australia. Vertex is consistently recognized as one
of the industry's top places to work, including being named to Science
magazine's Top Employers in the life sciences ranking for eight years in
a row. For additional information and the latest updates from the
company, please visit www.vrtx.com.

Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. KALYDECO®
(ivacaftor), ORKAMBI® (lumacaftor/ivacaftor), SYMDEKO™
(tezacaftor/ivacaftor and ivacaftor), VX-440, VX-152, VX-659 and VX-445
were discovered by Vertex as part of this collaboration.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, Dr. Chodakewitz's and Dr. Rowe's statements in the second
and third paragraphs, respectively, and the information provided
regarding the (i) timing and design of the Phase 3 study of VX-659,
tezacaftor and ivacaftor, (ii) potential to submit an NDA to the U.S.
FDA based on data from the initiated Phase 3 study and (iii) timing and
plans to initiate additional Phase 3 studies of triple combination
regimens containing VX-659 and/or VX-445. While Vertex believes the
forward-looking statements contained in this press release are accurate,
these forward-looking statements represent the company's beliefs only as
of the date of this press release, and there are a number of factors
that could cause actual events or results to differ materially from
those indicated by such forward-looking statements. Those risks and
uncertainties include that data from the Phase 3 development programs
may not support continued development or approval of the company's
triple-combination regimens due to safety, efficacy or other reasons,
and other risks listed under Risk Factors in Vertex's annual report and
quarterly reports filed with the Securities and Exchange Commission and
available through the company's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.